We will continue our studies on genetic variation of influenza viruses and on the mechanisms involved in these changes. The major focus will be on biochemical and genetic analysis of epidemiologically important strains isolated in nature. In addition, we will study genetic variation of influenza viruses following passage under different laboratory conditions. Three other areas of investigation will be pursued: the comparative biochemical analysis of the genomes of influenze A, B and C viruses, which includes nucleotide sequencing of specific genes, nucleic acid hybridization and the establishment of a genetic map for influenza C viruses; studies on the molecular cloning of influenza virus genes and their expression in pro- and eukaryotic cells; and attempts to select influenza virus mutants using recombinant DNA techniques.